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Chimerix Announces Final Data from AdVise Trial of Brincidofovir at BMT Tandem Meetings
-- Results show higher survival rate in adenovirus-infected patients with a virologic response to brincidofovir --
-- Mortality rates were lower in pediatric patients than in adult patients --
"The final data highlight the clinical benefit of the early antiviral effect of brincidofovir on adenovirus," said Dr.
The AdVise trial was an open-label, multicenter study designed to evaluate the efficacy, safety and overall tolerability of oral brincidofovir for the treatment of adenovirus infection. Pediatric and adult subjects were assigned to one of three cohorts:
- Cohort A, comprised of allogeneic HCT recipients with asymptomatic or limited adenovirus infection;
- Cohort B, comprised of allogeneic HCT recipients with disseminated adenovirus disease; and
- Cohort C, comprised of autologous HCT recipients, solid organ transplant recipients and other patients with serious adenovirus infections.
All subjects were to receive 12 weeks of oral brincidofovir and were followed for at least 36 weeks. This final analysis includes 158 allogeneic HCT recipients assigned to Cohorts A (23 adult and 42 pediatric patients) and B (35 adult and 58 pediatric patients).
In the AdVise trial, declines in AdV viral load of ≥2 log10 c/mL or below the limit of detection at Week 4 were observed in 76 percent of pediatric patients and 45 percent of adult patients. Notably, this antiviral effect was observed even in HCT recipients who did not yet have immune recovery. In Cohort A, 55 percent of patients with baseline low immunity (CD4 counts < 50 cells/μL) achieved ≥2 log10 c/mL decline or undetectable AdV at Week 4. In Cohort B, 52 percent of patients with baseline low immunity achieved ≥2 log10 c/mL decline or undetectable AdV over the same period of time.
In patients with disseminated disease, rapid virologic response, defined as undetectable AdV viremia at Week 6, was associated with nearly double the survival rate and lower adenovirus-associated mortality compared with subjects who did not have an antiviral response.
|Non-responder||7/13 (54%)||2/13 (15%)|
|Non-responder||13/14 (93%)||10/14 (71%)|
*Responders defined as subjects with baseline AdV viremia still on study at Week 6 who had undetectable plasma AdV at Week 6; non-responders defined as subjects who did not achieve the specified cut-off. A Cox model incorporating age group was used to compare mortality at 36 weeks in
responders and non-responders.
Diarrhea was the most commonly reported treatment emergent adverse event in the AdVise trial, reported in 38 percent of adult and 43 percent of pediatric HCT recipients. Many subjects enrolled in the AdVise trial, particularly in the first few months of the study, were begun on therapy at a point when they had multiple organ failure or other diagnoses likely to negatively impact their ability to survive the first four weeks of treatment. There was therefore a significant improvement in survival observed for subjects enrolled in the fourth quartile who were begun on brincidofovir with lower viral loads and a shorter time from AdV diagnosis to initiation of treatment. In the anticipated Study 999, patients who are unlikely to survive four weeks will not be enrolled in the trial.
"AdVise is the first
interventional trial in patients with serious adenovirus infections, a highly fatal disease after transplant. Because the median time to clear adenovirus from plasma in pediatric subjects was only 2-3 weeks, shorter courses of therapy with brincidofovir may deliver antiviral benefit and improve overall outcomes while limiting the risk of GI toxicity," said
Adenovirus (AdV) causes gastrointestinal and upper respiratory infections, including the common cold, in individuals with a functional immune system. However, in people with a weakened immune system, adenovirus can lead to life-threatening infections, including pneumonia and hepatitis. Pediatric and adult patients who have undergone allogeneic hematopoietic cell transplants (HCT) are at especially high risk for serious or fatal AdV infections due to profound immunodeficiency. Mortality rates of 50 to 80 percent have been reported in the literature for disseminated AdV disease. Rates of AdV infection with virus detected in the blood or other body fluids are higher in pediatric transplant recipients than in adults, and have resulted in many medical centers instituting screening protocols to detect AdV infection before the virus causes serious disease. There is currently no approved therapy for AdV infection, and although progression to disseminated disease in pediatric HCT recipients occurs in a small proportion of patients with AdV viremia, mortality rates for pediatric patients with confirmed AdV disease is greater than 50 percent in the first three months after diagnosis.
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the possibility that there may not be a viable continued development path for BCV, that any clinical trials we may conduct will not demonstrate adequate efficacy and safety of BCV, that enrollment in clinical trials we may
conduct may be insufficient or slower than we anticipate, that the FDA and other regulatory authorities may not approve BCV or BCV-based regimens, and that marketing approvals, if granted, may have significant limitations on their use. As a result, BCV may never be successfully commercialized. In addition, Chimerix may be unable to file for regulatory approval for BCV with other regulatory authorities. These risks, uncertainties and other factors could cause actual results to differ materially from those expressed or implied by such forward-looking statements. Risks are described more fully in the Company's filings with the
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